Allergic diseases are understood to be caused by production of IgE by an antigen stimulation invaded in a body, and successive release of various chemical mediators such as inflammatory cytokine, histamine, leukotriene and the like by a degranulation from an activated mast cell stimulated by a complex of the antigen and IgE, thereby constriction of airway, accentuation of vascular permeability, inflammation of skin, bronchi and the like are induced. Accordingly, antiallergic agents are understood mainly as drugs inhibiting allergic reaction type I and successively induced allergic inflammation, particularly as drugs inhibiting the production and release of the mediators from mast cells, or those as being antagonists against the aforementioned actions. At present, steroids, antihistaminic drugs, suppressants or inhibitors of the release of mediators and the like have been used as antiallergic agents. Although steroids are very effective drugs, they have a problem of side effects. Antihistaminic drugs are only for symptomatic therapies and fail to achieve radical therapy. Suppressants or inhibitors of the release of mediators are considered to have a high effectiveness. However, some of them lack immediate effectiveness or have central side effects. Accordingly, the antiallergic drugs currently available are not fully satisfactory as they are.
Patients with endometriosis are increasing in recent years, and currently, 10 to 14% of females are considered to be suffered from the disease. Endometriosis has been focused as a cause of sterility, as well as the disease lowers the quality of life of patients with severe pains during menstruation and coitus. For a treatment of the disease, a therapy by using a hormone drug has been currently applied as a pseudo menopausal therapy. However, the aforementioned therapy induces strong side effects, and it also has a risk of causing osteoporosis during a long-term administration. Therefore, at present, a drug or a method for treatment with safety and high efficacy is not available.
In recent years, it was found that mast cells exist apparently with high density in the lesion of endometriosis (American Journal of Reproductive Immunology (New York: 1998), (Denmark), Vol. 40, No. 4, p. 291-294), and that mast cells are activated to lead degranulation (Nikkei Medical, 2002, No. 415, p. 28; Fertility and Sterility, (USA), 2002, Vol. 78, No. 4, p. 782-786). Furthermore, a relation between endometriosis and allergy is strongly suggested, because interstitial hyperplasia, which is a major step of infiltration and lesion of mast cells, is significantly inhibited by the administration of a leukotriene antagonist having antiallergic action to an endometriosis model rat (Nikkei Medical, 2002, No. 415, p. 28; Fertility and Sterility, (USA), 2002, Vol. 78, No. 4, p. 782-786).
Therefore, an antiallergic drug, which strongly inhibits activation of mast cells and can be used as a therapeutic agent for radical treatment of allergic diseases, is usable as an effective therapeutic agent for endometriosis.
45% of patients with endometriosis are suffered from hysteromyoma, which suggests a relation of hysteromyoma and allergy in the same manner as endometriosis. Accordingly, it is highly probable that an antiallergic agent, which can be used as a therapeutic agent for radical treatment of allergic diseases, is useful as a therapeutic agent for hysteromyoma.
N-phenylsalicylamide derivatives are disclosed as a plant growth inhibitor in the specification of U.S. Pat. No. 4,358,443. As medicaments, said derivatives are disclosed as anti-inflammatory agents in the specification of European Patent No. 0,221,211, Japanese Patent Unexamined Publication (KOKAI) No. (Sho) 62-99329, and the specification of U.S. Pat. No. 6,117,859. Furthermore, they are disclosed as NF-κB inhibitors in the pamphlets of International Publication WO99/65499, International Publication WO02/49632, and International Publication WO02/076918, and as inhibitors against the production of cytokines in the pamphlet of International Publication WO02/051397.